Inhalational anthrax infection is associated with a 60-100% mortality rate, depending on the rapidity with which appropriate antimicrobial therapy is initiated. Experiments using an animal model of inhalational anthrax suggest that adjunctive therapy with equine-derived anti-anthrax antisera may be associated with higher survival rates, however no human-derived antisera have been previously available. This protocol provides a mechanism for obtaining high-titer anti-anthrax immunoglobulin by plasmapheresis of human volunteers who have recently received a course of anthrax vaccination. Volunteers are Department of Defense (DOD) employees and military personnel who are within 3 to 12 weeks of having received a fourth or greater dose of AVA if four to six total inoculations were given, or within 6 months of the last dose if seven or more AVA inoculations were given. All vaccinees were vaccinated as a requirement of their tour of duty and otherwise meet all blood donor eligibility criteria, in accord with Food and Drug Administration (FDA) requirements and American Association of Blood Banks (AABB) standards. Plasmapheresis was accomplished using licensed apheresis devices and standard collection techniques, and products meet all blood safety testing requirements mandated by the FDA. Plasma components collected under this protocol were stored in the frozen state as fresh frozen plasma (FFP) for possible administration to human patients critically ill with inhalational anthrax infection. Following collection of single donor FFP units, subsequent plasmapheresis components were stored frozen in liter-bottles for Cohn-Oncley fractionation, by a commercial fractionator, into an immunoglobulin preparation suitable for intravenous use, designated anthrax immune globulin intravenous (AIGIV). Intravenous administration of products derived from plasma collected under this protocol, whether as single-donor FFP or as AIGIV, will occur under a Phase I/II trial involving an Investigational New Drug (IND) exemption, with the IND held by the Centers for Disease Control and Prevention (CDC). The plasma products collected under this protocol may also be used in pharmacokinetic, dose finding, and efficacy studies in animals, and to establish a repository of reference serum standards at the CDC. During the period from 4/30/2002 to 9/30/2003, 38 recently AVA-vaccinated DoD employees underwent plasmapheresis at NIH to donate hyperimmune anti-anthrax plasma. Subjects underwent an average of 5.2 apheresis donations each, performed at weekly to biweekly intervals, yielding a total of 200 plasmapheresis components. During each session, 700-900 mL of plasma were collected, based on the individual's weight and approved FDA Guidelines for plasma collection. Fifty-four 250-300 mL bags of Anthrax Immune Plasma (AIP) were shipped to the CDC National Pharmaceutical Stockpile. A total of 140 liters of hyperimmune plasma, stored frozen in liter bottles, were provided to a contracted commercial manufacturer for further preparation into AIGIV.